Precision-cut Intestinal Slices as In Vitro Tool for Studies on Drug Metabolism

Abstract

The role of the intestine in drug metabolism has long been underestimated as a consequence of the technical difficulty to discern the role of the intestine from that of the liver in in vivo experiments and of the lack of in vitro models that are sufficiently viable and fully representing the physiology and anatomy of the intestine. Recently the precision-cut slice model, which is widely used for liver and kidney, was also adapted for the small and large intestine. In this review the application of precision-cut intestinal slices (PCIS) for research in drug metabolism and transport is discussed. PCIS can be prepared from animal and human tissues from all regions of the intestine allowing investigation of species differences and regional gradients of activities of metabolizing enzymes. They are viable for 8-24 h of incubation and show high activity of drug metabolizing enzymes, representative for the in vivo activity. They have been successfully used to study drug-drug interactions such as induction, inhibition and regulation of drug metabolizing enzymes, transporters and nuclear factors. Moreover they appear to be a suitable model for studies on cold preservation of donor organs for transplantation, and allow exploring inter-organ interactions by co-incubation with precision-cut slices of other organs. Their application as model for drug-induced intestinal toxicity is still in its infancy but appears to be promising. PCIS, prepared from human and animal tissues, represent a powerful translational model for drug metabolism, transport and toxicity studies and as such contributes to the reduction and replacement of animal experiments.